Psychiatric Genetics: Pharmacogenetics
Pharmacogenetics and pharmacogenomics of psychotropic drugs
Investigators: R.H. Segman, B. Lerer, A. Yakir. O. Agid
Pharmacogenetics is the study of genetic factors that influence response to drugs and the predisposition to develop adverse effects; pharmacogenomics involves the implementation of large-scale genomic approaches to this question. Our Laboratory is very interested in this topic and has initiated projects on the pharmacogenetics of antidepressant and antipsychotic drug response. Our most productive work in this field has been on tardive dyskinesia (TD), a serious long-term adverse effect of antipsychotic drugs. We are examining genetic influence on susceptibility to develop TD in a very carefully evaluated sample that has been collected in collaboration with other hospitals in Israel. We have identified significant contributions of the dopamine D3 receptor gene and a separate, additive contribution of the 5-HT2C receptor gene, to susceptibility to develop orofacial tardive dyskinesia.
5-HT2Cser and DRD3gly Allele Carriage in Schizophrenia Patient
with and without TD, and Matched Normal Controls
Adjusted mean AIMS orofacial dyskinesia scores (OFD) computed from ANOVA comparing patients carrying 1) 5-HT2Ccys and DRD3ser alleles (both wild type- WT), 2) 5-HT2Ccys and DRD3gly (WT+mutant), 3) 5-HT2Cser and DRD32cys (mutant +WT) or, 4) 5-HT2Cser and DRD32gly (mutant +mutant).
*p<.05 by planned comparison with 5-HT2Ccys and DRD3ser (both wild type- WT), #p<.05 vs. 5-HT2Ccys-DRD3gly.
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